Reumann MK, Strachna O, Lukashova L, Verdelis K, Donnelly E, Boskey AL, and Mayer-Kuckuk P. (2011) Early growth response gene-1 regulates bone properties in mice. Calcif Tissue Int 89:1-9.

DOI

Abstract

Transcriptional regulation of the postnatal skeleton is incompletely understood. Here, we determined the consequence of loss of early growth response gene 1 (EGR-1) on bone properties. Analyses were performed on both the microscopic and molecular levels utilizing micro-computed tomography (micro-CT) and Fourier transform infrared imaging (FTIRI), respectively. Mice deficient in EGR-1 (Egr-1 −/−) were studied and compared to sex- and age-matched wild-type (wt) control animals. Femoral trabecular bone in male Egr-1 −/− mice demonstrated osteopenic characteristics marked by reductions in both bone volume fraction (BV/TV) and bone mineral density (BMD). Morphological analysis revealed fewer trabeculae in these animals. In contrast, female Egr-1 −/− animals had thinner trabeculae, but BV/TV and BMD were not significantly reduced. Analysis of femoral cortical bone at the mid-diaphysis did not show significant osteopenic characteristics but detected changes in cross-sectional geometry in both male and female Egr-1 −/− animals. Functionally, this resulted in decreased resistance to three-point bending as indicated by a reduction in maximum load, failure load, and stiffness. Assessment of compositional bone properties, including mineral-to-matrix ratio, carbonate-to-phosphate ratio, crystallinity, and cross-linking, in femurs by FTIRI did not show any significant differences or an appreciable trend between Egr-1 −/− and wt mice of either sex. Unexpectedly, rib bone from Egr-1 −/− animals displayed distinct osteopenic traits that were particularly pronounced in female mice. This study provides genetic evidence that both sex and skeletal site are critical determinants of EGR-1 activity in vivo and that its site-specific action may contribute to the mechanical properties of bone.

Keywords

Transcription factor; Early growth response gene 1; Mice; Micro-computed tomography; Biomechanics

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